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Show contents of the paper.
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[001/124] Abstract
[002/124] Allele-specific silencing by...
[003/124] Introduction
[004/124] Autosomal dominant adult-onset...
[005/124] At the cellular...
[006/124] In recent years,...
[007/124] However, a major...
[008/124] Other than a...
[009/124] In this study,...
[010/124] Compared to other...
[011/124] Since ADLD patients...
[012/124] Figure 1
[013/124] Overview of the...
[014/124] Overview of the...
[015/124] To the best...
[016/124] Materials and methods
[017/124] Plasmid vectors are...
[018/124] Cell lines and cell culture
[019/124] Fibroblast cell lines...
[020/124] The HEK293T cells...
[021/124] Primary oligodendrocyte precursor...
[022/124] Design of siRNAs and generation of shRNA recombinant lentivirus particles
[023/124] We designed an...
[024/124] The most efficient...
[025/124] Dual luciferase reporter assay
[026/124] HEK293T cells were...
[027/124] Validation of allele-specific siRNAs in ADLD fibroblasts
[028/124] ADLD and control...
[029/124] To evaluate the...
[030/124] Direct reprogramming of ADLD and control human fibroblasts in neurons
[031/124] Viral production and titration
[032/124] HEK293NT cells were...
[033/124] The virus was...
[034/124] Direct neuronal reprogramming
[035/124] Low-passage primary human...
[036/124] Validation of allele-specific shRNAs in ADLD neurons
[037/124] Cells were transduced...
[038/124] Validation of allele-specific shRNAs in rat oligodendrocytes cultures overexpressing human LMNB1 coding sequence
[039/124] After the shaking...
[040/124] RNA isolation and quantitative real time PCR
[041/124] Total RNA was...
[042/124] Reactions were carried...
[043/124] Allelic discrimination by primer extension assay
[044/124] To evaluate the...
[045/124] Western blot analysis
[046/124] Total protein was...
[047/124] Immunofluorescence
[048/124] Fibroblasts
[049/124] Cells were plated...
[050/124] Reprogrammed neurons and primary oligodendrocyte precursors cell cultures
[051/124] Reprogrammed neurons and...
[052/124] In a set-up...
[053/124] Note that because...
[054/124] Upon transfection with...
[055/124] Statistical analysis
[056/124] Graphics and statistical...
[057/124] Data availability
[058/124] The authors confirm...
[059/124] Results
[060/124] Identification of allele-specific siRNAs
[061/124] To exploit the...
[062/124] Bioinformatics tools that...
[063/124] Figure 2
[064/124] ASP-siRNA screening. (A)...
[065/124] ASP-siRNA screening. (A)...
[066/124] The results are...
[067/124] ASP-siRNAs restored physiological LMNB1 levels and ameliorated ADLD cellular phenotypes in patient fibroblasts
[068/124] Human ADLD fibroblasts...
[069/124] We evaluated the...
[070/124] Figure 3
[071/124] Primary readouts of...
[072/124] Primary readouts of...
[073/124] We accurately evaluated...
[074/124] Next, we verified...
[075/124] Furthermore, to evaluate...
[076/124] By fluorescent microscopy,...
[077/124] Figure 4
[078/124] Secondary readouts of...
[079/124] Secondary readouts of...
[080/124] To evaluate transcriptome...
[081/124] ASP-siRNA treatment ameliorated ADLD-specific cellular phenotypes in disease-relevant cellular models
[082/124] Disease-relevant cellular and...
[083/124] Validation of the therapeutic potential of ASP-siRNA in reprogrammed ADLD neurons
[084/124] Fibroblasts from three...
[085/124] To validate our...
[086/124] Figure 5
[087/124] Validation of ASP-RNAi...
[088/124] Validation of ASP-RNAi...
[089/124] Validation of the therapeutic potential of ASP-siRNA in rat oligodendrocyte cultures overexpressing hLMNB1
[090/124] Primary OPCs were...
[091/124] OPCs overexpressing the...
[092/124] Figure 6
[093/124] Validation of ASP-RNAi...
[094/124] Validation of ASP-RNAi...
[095/124] Discussion
[096/124] ADLD is a...
[097/124] As ADLD is...
[098/124] We reasoned that...
[099/124] ADLD patients have...
[100/124] Identification of efficient...
[101/124] Thus, we planned...
[102/124] Beyond their structural...
[103/124] Overall, our results...
[104/124] To demonstrate ASP-silencing...
[105/124] Both cellular models...
[106/124] The treatment reduced...
[107/124] ADLD is a...
[108/124] Following these results,...
[109/124] To overcome this...
[110/124] Delivery of ASP-siRNAs...
[111/124] Our work represents...
[112/124] Genetic diseases associated...
[113/124] Question marks indicate...
[114/124] Genetic diseases associated...
[115/124] Question marks indicate...
[116/124] Overall, our work...
[117/124] autosomal dominant adult-onset...
[118/124] allele-specific silencing by...
[119/124] oligodendrocyte precursor cell...
[120/124] single nucleotide polymorphism...
[121/124] We thank Dr...
[122/124] The work was...
[123/124] A.Br. and E.G....
[124/124] Supplementary data
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